1Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Mar 153B: 428-37
TitleImpact of Neuritin 1 (NRN1) polymorphisms on fluid intelligence in schizophrenia.
AbstractNeuritin 1 (NRN1), an activity-regulated gene with multiple roles in neurodevelopment and synaptic plasticity, is located within the 6p24-p25 interval on chromosome 6, previously identified as linked to a subtype of schizophrenia (SZ) characterized by pervasive cognitive deficit (CD). We have tested the effect of NRN1 sequence variation on susceptibility to SZ and on general cognitive ability in patients and non-psychiatric control subjects by re-sequencing the coding regions of NRN1 and its flanking sequences, and genotyping 19 single-nucleotide polymorphisms (SNPs) in 336 SZ patients and 172 healthy control individuals. All participants completed comprehensive neurocognitive assessment, including tests estimating premorbid/prior IQ and current IQ. Logistic regression analyses found no significant association for any of the 19 SNPs with SZ or its CD subtype. However, linear regression analysis gave significant association (P = 0.024 and P = 0.027 after correction for multiple testing) for polymorphisms rs1475157 and rs9405890 with current IQ in the patient group. In SZ, the rs1475157-rs9405890 haplotypes revealed a highly significant association with the abstraction component of current ("fluid") intelligence (P = 0.0014), and with percentage loss of IQ points between premorbid and current intelligence (P = 0.0041). Results in the control group were not significant after correction. This is the first analysis of association between variation in NRN1 and SZ. The findings suggest a role of NRN1 as a modifier of cognitive functioning in SZ, with implications for future research into the impact of the environment on the development and maintenance of "fluid" intelligence.
SCZ Keywordsschizophrenia
2Eur J Med Genet 2015 May 58: 310-8
TitleSubtelomeric 6p25 deletion/duplication: Report of a patient with new clinical findings and genotype-phenotype correlations.
AbstractThe 6p terminal deletions are rare and present variability of clinical features, which increases the importance of reporting additional cases in order to better characterize genotype-phenotype correlations. We report a 12-year-old girl with a de novo deletion in 6p25.1-pter characterized by high-resolution karyotyping and FISH. Further analysis using oligonucleotide array-CGH revealed a 5.06Mb 6p25.1-pter deletion associated with a contiguous 1Mb 6p25.1 duplication. The patient presented normal growth, developmental delay, frontal bossing, severe hypertelorism, corectopia, wide and depressed nasal bridge, mild learning disability, hearing loss and diffuse leukopathy. Additionaly, she presented peculiar phenotypic features reported herein for the first time in 6p25 deletion syndrome: cerebrospinal fluid fistula and bones resembling those seen in 3-M syndrome. The distinctive phenotype of the 6p25 deletion syndrome has been mainly correlated with the FOXC1 and FOXF2 genes deletions, both related mainly to eye development. We also consider the SERPINB6 as a candidate for sensorineural hearing loss and TUBB2A as a candidate for our patient's skeletal features. In addition, as our patient had a duplication including NRN1, a gene related with neurodevelopment, synaptic plasticity and cognitive dysfunction in schizophrenia, we suggest that this gene could be associated with her white matter abnormalities and neurocognitive phenotype.
SCZ Keywordsschizophrenia
3World J. Biol. Psychiatry 2016 Mar 17: 129-39
TitleInvolvement of NRN1 gene in schizophrenia-spectrum and bipolar disorders and its impact on age at onset and cognitive functioning.
AbstractObjectives Neuritin 1 gene (NRN1) is involved in neurodevelopment processes and synaptic plasticity and its expression is regulated by brain-derived neurotrophic factor (BDNF). We aimed to investigate the association of NRN1 with schizophrenia-spectrum disorders (SSD) and bipolar disorders (BPD), to explore its role in age at onset and cognitive functioning, and to test the epistasis between NRN1 and BDNF. Methods The study was developed in a sample of 954 SSD/BPD patients and 668 healthy subjects. Genotyping analyses included 11 SNPs in NRN1 and one functional SNP in BDNF. Results The frequency of the haplotype C-C (rs645649-rs582262) was significantly increased in patients compared to controls (P?=?0.0043), while the haplotype T-C-C-T-C-A (rs3763180-rs10484320-rs4960155-rs9379002-rs9405890-rs1475157) was more frequent in controls (P?=?3.1??10(-5)). The variability at NRN1 was nominally related to changes in age at onset and to differences in intelligence quotient, in SSD patients. Epistasis between NRN1 and BDNF was significantly associated with the risk for SSD/BPD (P?=?0.005). Conclusions Results suggest that: (i) NRN1 variability is a shared risk factor for both SSD and BPD, (ii) NRN1 may have a selective impact on age at onset and intelligence in SSD, and (iii) the role of NRN1 seems to be not independent of BDNF.
SCZ Keywordsschizophrenia